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Mycobacterium abscessus

  • Rifabutin Is Inactivated by <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span> Arr
    Mechanisms of Resistance
    Rifabutin Is Inactivated by Mycobacterium abscessus Arr

    Mycobacterium abscessus exhibits arr (ADP-ribosyltransferase)-dependent rifampin resistance. In apparent contrast, rifabutin (RBT) has demonstrated promising activity in M. abscessus infection models, implying that RBT might not be inactivated by Arr.

    Daniel Schäfle, Petra Selchow, Barbara Borer, Michael Meuli, Anna Rominski, Bettina Schulthess, Peter Sander
  • Differential <em>In Vitro</em> Activities of Individual Drugs and Bedaquiline-Rifabutin Combinations against Actively Multiplying and Nutrient-Starved <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span>
    Experimental Therapeutics
    Differential In Vitro Activities of Individual Drugs and Bedaquiline-Rifabutin Combinations against Actively Multiplying and Nutrient-Starved Mycobacterium abscessus

    Current treatment options for lung disease caused by Mycobacterium abscessus complex infections have limited effectiveness. To maximize the use of existing antibacterials and to help inform regimen design for treatment, we assessed the in vitro bactericidal activity of single drugs against actively multiplying and net nonreplicating...

    Jin Lee, Nicole Ammerman, Anusha Agarwal, Maram Naji, Si-Yang Li, Eric Nuermberger
  • First Penicillin-Binding Protein Occupancy Patterns for 15 β-Lactams and β-Lactamase Inhibitors in <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span>
    Pharmacology
    First Penicillin-Binding Protein Occupancy Patterns for 15 β-Lactams and β-Lactamase Inhibitors in Mycobacterium abscessus

    Mycobacterium abscessus causes serious infections that often require over 18 months of antibiotic combination therapy. There is no standard regimen for the treatment of M. abscessus infections, and the multitude of combinations that have been used clinically have had low success rates and high rates...

    Alaa R. M. Sayed, Nirav R. Shah, Kari B. Basso, Manasi Kamat, Yuanyuan Jiao, Bartolome Moya, Dhruvitkumar S. Sutaria, Yinzhi Lang, Xun Tao, Weiguo Liu, Eunjeong Shin, Jieqiang Zhou, Carolin Werkman, Arnold Louie, George L. Drusano, Jürgen B. Bulitta
  • Rifabutin Is Bactericidal against Intracellular and Extracellular Forms of <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span>
    Mechanisms of Action: Physiological Effects
    Rifabutin Is Bactericidal against Intracellular and Extracellular Forms of Mycobacterium abscessus

    Mycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases. As it is intrinsically resistant to most conventional antibiotics, there is an unmet medical need for effective treatments. Repurposing of clinically validated pharmaceuticals represents an attractive option for the development of chemotherapeutic...

    Matt D. Johansen, Wassim Daher, Françoise Roquet-Banères, Clément Raynaud, Matthéo Alcaraz, Florian P. Maurer, Laurent Kremer
  • Open Access
    AR-12 Exhibits Direct and Host-Targeted Antibacterial Activity toward <em>Mycobacterium abscessus</em>
    Susceptibility
    AR-12 Exhibits Direct and Host-Targeted Antibacterial Activity toward Mycobacterium abscessus

    Therapeutic options for Mycobacterium abscessus infections are extremely limited. New or repurposed drugs are needed. The anti-M. abscessus activity of AR-12 (OSU-03012), reported to express broad-spectrum antimicrobial effects, was investigated in vitro and in vivo. Antimicrobial...

    Shaoyan Zhang, Yuzhen Zou, Qi Guo, Jianhui Chen, Liyun Xu, Xiaoyu Wan, Zhemin Zhang, Bing Li, Haiqing Chu
  • Open Access
    Insights into the <span class="sc">l</span>,<span class="sc">d</span>-Transpeptidases and <span class="sc">d</span>,<span class="sc">d</span>-Carboxypeptidase of <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span>: Ceftaroline, Imipenem, and Novel Diazabicyclooctane Inhibitors
    Mechanisms of Resistance
    Insights into the l,d-Transpeptidases and d,d-Carboxypeptidase of Mycobacterium abscessus: Ceftaroline, Imipenem, and Novel Diazabicyclooctane Inhibitors

    Mycobacterium abscessus is a highly drug-resistant nontuberculous mycobacterium (NTM). Efforts to discover new treatments for M. abscessus infections are accelerating, with a focus on cell wall synthesis proteins (M. abscessus...

    Khalid M. Dousa, Sebastian G. Kurz, Magdalena A. Taracila, Tracey Bonfield, Christopher R. Bethel, Melissa D. Barnes, Suresh Selvaraju, Ayman M. Abdelhamed, Barry N. Kreiswirth, W. Henry Boom, Shannon H. Kasperbauer, Charles L. Daley, Robert A. Bonomo
  • Efficacy of Bedaquiline, Alone or in Combination with Imipenem, against <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span> in C3HeB/FeJ Mice
    Experimental Therapeutics
    Efficacy of Bedaquiline, Alone or in Combination with Imipenem, against Mycobacterium abscessus in C3HeB/FeJ Mice

    Mycobacterium abscessus lung infections remain difficult to treat. Recent studies have recognized the power of new combinations of antibiotics, such as bedaquiline and imipenem, although in vitro data have questioned this combination. We report that the efficacy of bedaquiline-imipenem combination treatment relies essentially on the activity of bedaquiline in...

    Vincent Le Moigne, Clément Raynaud, Flavie Moreau, Christian Dupont, Jérôme Nigou, Olivier Neyrolles, Laurent Kremer, Jean-Louis Herrmann
  • Synergistic Interactions of Indole-2-Carboxamides and β-Lactam Antibiotics against <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span>
    Mechanisms of Action: Physiological Effects
    Synergistic Interactions of Indole-2-Carboxamides and β-Lactam Antibiotics against Mycobacterium abscessus

    New drugs or therapeutic combinations are urgently needed against Mycobacterium abscessus. Previously, we demonstrated the potent activity of indole-2-carboxamides 6 and 12 against M. abscessus. We show here that these compounds act synergistically with imipenem and cefoxitin in vitro and...

    Clément Raynaud, Wassim Daher, Françoise Roquet-Banères, Matt D. Johansen, Jozef Stec, Oluseye K. Onajole, Diane Ordway, Alan P. Kozikowski, Laurent Kremer
  • KatG as Counterselection Marker for Nontuberculous Mycobacteria
    Letter to the Editor
    KatG as Counterselection Marker for Nontuberculous Mycobacteria
    Aron Gagliardi, Petra Selchow, Sakshi Luthra, Daniel Schäfle, Bettina Schulthess, Peter Sander
  • Open Access
    TBAJ-876, a 3,5-Dialkoxypyridine Analogue of Bedaquiline, Is Active against <span class="named-content genus-species" id="named-content-1">Mycobacterium abscessus</span>
    Experimental Therapeutics
    TBAJ-876, a 3,5-Dialkoxypyridine Analogue of Bedaquiline, Is Active against Mycobacterium abscessus

    Lung disease caused by Mycobacterium abscessus is very difficult to cure, and treatment failure rates are high. The antituberculosis drug bedaquiline (BDQ) is used as salvage therapy against this dreadful disease. However, BDQ is highly lipophilic, displays a long terminal half-life, and presents a cardiotoxicity liability associated with QT interval prolongation....

    Jickky Palmae Sarathy, Uday S. Ganapathy, Matthew D. Zimmerman, Véronique Dartois, Martin Gengenbacher, Thomas Dick

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